Mixed Invasive Pulmonary Mucor and Aspergillus Infection: A Case Report and Literature Review
Invasive fungal infections represent a significant clinical challenge, particularly in immunocompromised patients. This case report details a rare coinfection of invasive pulmonary mucormycosis (IPM) and invasive pulmonary aspergillosis (IPA) in a 54-year-old woman with uncontrolled type 2 diabetes mellitus. The case highlights diagnostic complexities, therapeutic challenges, and the critical role of histopathology and imaging in guiding management.
Clinical Presentation and Initial Management
The patient presented with an 8-day history of nausea, vomiting, and diabetic ketoacidosis (DKA). Her medical history included a decade-long diagnosis of poorly controlled type 2 diabetes. Initial vital signs indicated hypotension (83/63 mmHg) and tachycardia (104 beats/min). Laboratory findings revealed severe metabolic acidosis (pH 6.94), hyperglycemia (29.4 mmol/L), leukocytosis (17.06 × 10⁹/L), and elevated C-reactive protein (35.59 mg/L). Renal impairment was evident, with serum creatinine at 120.92 mmol/L and urea nitrogen at 18.0 mmol/L.
Chest computed tomography (CT) on admission showed multiple nodules in the right lung. Initial empiric antibiotic therapy with levofloxacin and cefminox was administered but failed to resolve symptoms. A follow-up CT scan on day 5 revealed air crescent signs in the right upper lobe, bilateral pulmonary infiltration, and pleural effusion. Despite escalation to biapenem and levofloxacin, the patient developed persistent fever and worsening respiratory symptoms.
Diagnostic Challenges and Bronchoscopic Findings
By day 23, bronchoscopy identified stenosis and mucosal edema in the right middle bronchus, accompanied by white moss-like lesions and friable mucosa. Serum galactomannan (GM) testing returned a positive result (0.92 mg/L; cutoff: 0.65 mg/L), prompting suspicion of IPA. Voriconazole therapy (400 mg intravenous loading dose followed by 200 mg twice daily) was initiated. However, clinical improvement was transient, with recurrent fever and progression of pulmonary lesions on repeat imaging.
A second bronchoscopy on day 29 demonstrated near-complete obstruction of the right middle bronchus. Histopathological examination of biopsied tissue identified Mucor hyphae, confirming IPM. Subsequent BALF and serum GM levels normalized (0.41 mg/L and 0.64 mg/L, respectively), but clinical deterioration necessitated a switch to amphotericin B (AmB). Renal toxicity from AmB led to substitution with liposomal AmB (dose escalated from 20 mg/day to 120 mg/day). Despite 11 days of therapy, clinical and radiological progression persisted, prompting the addition of oral posaconazole (10 mg twice daily).
Surgical Intervention and Histopathological Confirmation
Serial CT scans and bronchoscopy between days 52 and 57 revealed unabated disease progression. Given the failure of medical therapy and concerns over lung function preservation, a right middle and lower lobectomy was performed. Gross examination of the resected specimen demonstrated fungal clusters and abscesses. Histopathology confirmed coinfection with Aspergillus (fine, septate hyphae with acute-angle branching on Grocott’s methenamine silver stain) and Mucor (broad, aseptate hyphae with right-angled branching on periodic acid-Schiff stain).
Postoperative Recovery and Follow-Up
Following lobectomy, the patient’s condition stabilized, with resolution of fever and normalization of inflammatory markers. Postoperative bronchoscopy confirmed mucosal healing without residual lesions. The patient was discharged on day 78 with continued posaconazole therapy and regular outpatient monitoring.
Discussion of Key Clinical and Diagnostic Insights
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Risk Factors and Pathogenesis: Uncontrolled diabetes, particularly with DKA, is a major risk factor for invasive fungal infections. Hyperglycemia impairs neutrophil function, including reactive oxygen species (ROS) production, which is critical for combating Aspergillus. Mucor species thrive in acidic environments, such as those seen in DKA, facilitating tissue invasion.
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Imaging Features: The air crescent sign, observed on day 5, is classically associated with IPA and reflects necrotic lung tissue retraction. However, this sign is not pathognomonic and may also occur in bacterial infections or malignancies. Rapid progression to atelectasis and lobar consolidation, as seen in this case, underscores the aggressive nature of dual fungal infections.
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Role of Galactomannan Testing: Serum GM testing provided an early clue to Aspergillus infection, with a peak level of 0.92 mg/L. However, BALF GM levels were more sensitive for localized disease. Normalization of GM levels post-voriconazole correlated with reduced fungal burden but did not account for concurrent Mucor infection, emphasizing the need for histopathological confirmation.
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Therapeutic Dilemmas: The case illustrates challenges in balancing antifungal efficacy with toxicity. Amphotericin B remains first-line for mucormycosis, but nephrotoxicity often limits its use. Liposomal formulations offer improved safety profiles, though suboptimal tissue penetration may explain treatment failure in this patient. Posaconazole, with broad-spectrum activity, served as salvage therapy but required surgical debridement to achieve cure.
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Histopathological Diagnosis: Coinfection was definitively diagnosed only after lobectomy. Aspergillus hyphae (3–6 μm diameter, septate) and Mucor hyphae (6–25 μm diameter, aseptate) were morphologically distinct on staining. This underscores the limitations of culture-based methods, as respiratory specimens often fail to grow Mucorales.
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Literature Context: Among 11 reported cases of IPM-IPA coinfection, diabetes accounted for 27%. Mortality in such cases exceeds 50%, driven by delayed diagnosis and comorbidities. Early bronchoscopy, GM monitoring, and aggressive imaging are critical for timely intervention.
Conclusion
This case underscores the lethal potential of mixed invasive fungal infections in immunocompromised hosts. Dual infections necessitate a high index of suspicion, particularly when monotherapy fails. Serial GM testing, bronchoscopy, and CT imaging are indispensable for early diagnosis, while histopathology remains the gold standard. Surgical resection, combined with tailored antifungal regimens, can improve outcomes in refractory cases. Clinicians must remain vigilant for coinfections in high-risk populations, such as diabetics with unresolved pulmonary infiltrates.
doi.org/10.1097/CM9.0000000000001839
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